The NADP-dependent glutamate dehydrogenase of Saccharomyces cerevisiae is inactivated when cultures are starved of glucose. Specific antiserum was prepared against the purified enzyme and used to quantitate enzyme levels during inactivation. A parallel loss of antigen and enzyme activity was observed. An in vitro NADP-dependent glutamate dehydrogenase inactivating system was obtained using lysed vacuoles and also preincubating yeast extracts at pH 5. The inactivating activity was stimulated by the addition of protein precipitating agents, such as ammonium sulfate, sodium sulfate and polyethylene glycol. From experiments using specific protease inhibitors it was concluded that the in vitro inactivating activity is protease B.